USE OF FLUOROQUI NOLONES EMEA/ CVMP/ SAGAM/ 1 8 4 6 5 1 / 2 0 0 5 - - PowerPoint PPT Presentation

12th Oct 2006 12th Oct 2006 EMEA Int. Parties Meeting EMEA Int. Parties Meeting

COMMENTS of COMMENTS of the the ASSOCIATION OF VETERINARY ASSOCIATION OF VETERINARY CONSULTANTS CONSULTANTS Presented Presented by by Dr. Klaus Hellmann (VP)

• Dr. Klaus Hellmann (VP)

USE OF FLUOROQUI NOLONES EMEA/ CVMP/ SAGAM/ 1 8 4 6 5 1 / 2 0 0 5 – CONSULTATI ON

12th Oct 2006 12th Oct 2006 EMEA Int. Parties Meeting EMEA Int. Parties Meeting

AVC AVC

• VETERINARIANS

VETERINARIANS

• CONSULTANTS

CONSULTANTS

– – Veterinary Veterinary Medicinal Medicinal Products Products

• Quality

Quality, , Safety Safety and and Efficacy Efficacy

– – Feed Feed / / Feed Feed Additives Additives – – Food Food

• 44 EXPERTS (

44 EXPERTS ( most most from from Europe) Europe)

• ETHICAL and SCIENTIFIC CODE

ETHICAL and SCIENTIFIC CODE

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AVC RESPONSE AVC RESPONSE

• AVC agrees with the concept that antimicrobials should be

AVC agrees with the concept that antimicrobials should be used wisely, within a rational programme, and that it is used wisely, within a rational programme, and that it is preferable and important to reserve critical antimicrobials preferable and important to reserve critical antimicrobials for those conditions where their use can be justified on the for those conditions where their use can be justified on the grounds that only they are likely to have a positive clinical grounds that only they are likely to have a positive clinical

• r animal welfare impact
• r animal welfare impact
• Quinolones

Quinolones and fluoroquinolones are not comparable or and fluoroquinolones are not comparable or equal in terms of their usage in the EU or their equal in terms of their usage in the EU or their breakpoints in different species, conditions and body breakpoints in different species, conditions and body

• compartments. Therefore, we believe it is misleading and
• compartments. Therefore, we believe it is misleading and

potentially damaging to use potentially damaging to use quinolones quinolones alone as the alone as the benchmarks for decisions on fluoroquinolones, except benchmarks for decisions on fluoroquinolones, except possibly for campylobacter. possibly for campylobacter.

• The entire topic of breakpoints is one that deserves

The entire topic of breakpoints is one that deserves separate discussion. separate discussion.

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Importance of Fluoroquinolones in Importance of Fluoroquinolones in food food-

• producing animals

producing animals

• They m ay be the only effective class of

They m ay be the only effective class of drugs drugs

– – Colisepticaemia Colisepticaemia in turkeys in turkeys – – Colisepticaemia Colisepticaemia in broilers in broilers – – Colisepticaemia Colisepticaemia in newborn calves in newborn calves – – Colisepticaemia Colisepticaemia in piglets in piglets – – A.

• A. pleuropneumoniae

pleuropneumoniae in in pigs pigs – – E. coli

• E. coli mastitis

mastitis

• Tissue distribution and penetration unique

Tissue distribution and penetration unique

• Essential for treatm ent of anim als w ith life

Essential for treatm ent of anim als w ith life-

• threatening diseases

threatening diseases

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Use Use of Fluoroquinolones

• f Fluoroquinolones
• The

The influence influence of

• f veterinary

veterinary use use on

• n

antimicrobial antimicrobial resistance resistance in in humans humans is is likely likely to to be be very very low low

• AVC believes that farm anim al use of

AVC believes that farm anim al use of fluoroquinolones is probably a m inor fluoroquinolones is probably a m inor relevant source of resistance in term s of relevant source of resistance in term s of im pact on hum ans im pact on hum ans

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Use Use of Fluoroquinolones

• f Fluoroquinolones
• Although

Although relevant relevant data data is is presented presented, , more more data data is is needed needed from from individual individual countries countries and and set set in in relation relation to MA to MA for for Fluoroquinolones Fluoroquinolones present present

• Patent situation m ay be used as

Patent situation m ay be used as guide: guide:

– – Markets Markets with with extensive extensive use use since since 15 15 years years – – Markets Markets with with limited limited use use

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Amount Amount of

• f use

use of FQ in

• f FQ in non

non-

• regulated

regulated markets markets

• Dependent

Dependent on

• n availability

availability of

• f

„ „ generic generic/ / cheap cheap“ “ products products: :

– – e.g e.g. . various various Eastern European MS Eastern European MS – – e.g e.g. Spain/ Portugal . Spain/ Portugal

• Generics

Generics available available for for 15 15 years years

• Prices

Prices per per unit unit very very low low ( ( 10 % of 10 % of reference reference) )

• High

High use use of

• f FQs

FQs in in poultry poultry and and swine swine

• Broad

Broad use use as as preventional preventional treatment treatment

• High

High rates rates of

• f resistance

resistance

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Use Use of FQ in

• f FQ in regulated

regulated markets markets

• E.g

E.g. Germany, UK, DK . Germany, UK, DK

– – FQ FQ are are high high priced priced products products – – Well Well controlled controlled, , prescription prescription only

• nly since

since launch launch – – Relatively Relatively low low use use, , mainly mainly therapeutic therapeutic/ / treatment treatment – – Low Low rates rates of

• f resistance

resistance

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Danmap Danmap 2004 2004

0,06* 0,06* 98,1 % 98,1 % 0,06 0,06 100 % 100 % 0,06 0,06 100 % 100 % Salm. Salm. spp spp 0,03 0,03 96,6 % 96,6 % 0,03 0,03 100 % 100 % 0,12 0,12 88 % 88 % E.

• E. Coli

Coli Swine Swine µg/ ml µg/ ml Cattle Cattle µg/ ml µg/ ml Chicken Chicken µg/ ml µg/ ml MIC MIC90

90

% sensitive % sensitive Breakpoint used: 0,03 µg/ ml, Including broilers and layers * Highest MIC measured: 0,5 µg/ ml

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Germany Germany

16* 16* 72,1 % 72,1 % 0,016# 0,016# 100 % 100 % Cattle Cattle µg/ ml µg/ ml 0,06 0,06-

• 0,5*

0,5* 92 92-

• 98 %

98 % 0,06* * 0,06* * N= 187 N= 187 0,5* 0,5* ~ 98 % ~ 98 % MIC MIC90

90

% sensitive % sensitive

0,016# 0,016# 100 % 100 % 0,06* 0,06* 98 % 98 % 0,016# 0,016# 96 % 96 % MIC MIC90

90

% sensitive % sensitive

Swine Swine µg/ ml µg/ ml Dairy Dairy M M µg/ ml µg/ ml Chicken Chicken µg/ ml µg/ ml E.

• E. Coli

Coli

* Wallmann, Kroker: 3rd Conf Vet Antimicrobials, Orlando, USA, 2006; * * Krabisch und Gangl, TU 2002; # De Jong et al., ICAAC 2006 (Abattoirs samples)

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Portugal / Spain Portugal / Spain

0,25 0,25 98 % 98 % 8 8 76,5 % 76,5 % Spain# Spain# 16* 16* 76,9 % 76,9 % 64* 64* 56,9 % 56,9 % 32* 32* 50,8 % 50,8 % MIC MIC90

90

% sensitive % sensitive

Swine Swine µg/ ml µg/ ml Calves Calves µg/ ml µg/ ml Chicken Chicken µg/ ml µg/ ml E.

• E. Coli

Coli

Various Fluoroquinolones marketed including Generics * Baptista et al. (2006): 11 EAVPT, Torino, 2006; Breakpoint used: 4µg/ ml # De Jong et al., ICAAC 2006 (Abattoirs samples)

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Hungary Hungary

• Fluoroquinolones since 1989, first

generic licensed 1991

• ~ 25 % of antibiotics used in animal

health are now Fluoroquinolones

• Prices reduced from 75 to 5, same time

use up by 750% , 100 being Baytril

• No public data on resistance

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Consequence Consequence? ?

Increase the price? Can it be that simple?

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Off Label Off Label Use Use/Illegal /Illegal Use Use

Care needs to be taken by over-regulating

the market! E.g. Illegal use of nitrofurans in food animals: contribution to human salmonellosis* (Portugal): 65 % of Samonella isolates from several sources (most human and poultry) with decreased susceptibility, most S. enteritidis

* Antunes et al. (2006) Clinical Microbiology and Infection

12th Oct 2006 12th Oct 2006 EMEA Int. Parties Meeting EMEA Int. Parties Meeting

C.

• C. jejuni

jejuni and C. and C. coli coli

AVC is critical to the Delsol et al (2004) study on

Campylobacter coli described in the document, in that it was monitored for only 5 weeks after treatment and not followed through to slaughter

AVC stresses that care needs to be taken in relating

experimental studies such as Delsol et al (2004) to practical situations

AVC disagrees with the statement that ‘In the

developed countries most human infections with Campylobacter and Salmonella are food borne’

Propose to consider C. jejuni and C. coli separately

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Selection Selection for for Resistance Resistance

• AVC completely disagrees with the

AVC completely disagrees with the statement referring to statement referring to ‘Their ‘Their potential of relatively rapid potential of relatively rapid selection of resistance’ selection of resistance’ ( ( problems problems

• nly
• nly in

in non non-

• regulated

regulated markets markets) )

• In

In fact fact there there is is low low rate rate for for selection selection, as , as found found in in most most slaughter slaughter house house surveys surveys

12th Oct 2006 12th Oct 2006 EMEA Int. Parties Meeting EMEA Int. Parties Meeting

Problems Problems

• No

No harm onised approach harm onised approach in the in the conditions of use of ( conditions of use of ( fluoro fluoro-

• )quinolones

)quinolones in in EU EU

• ‘Antimicrobial resistance should be

‘Antimicrobial resistance should be addressed internationally, as resistant addressed internationally, as resistant bacteria can spread via imported food’, it bacteria can spread via imported food’, it should be added: ‘ should be added: ‘and infections can be and infections can be contracted by foreign travel as high contracted by foreign travel as high-

• lighted in

lighted in Danm ap Danm ap 2 0 0 4 ; in such 2 0 0 4 ; in such foreign foreign-

• acquired situations,

acquired situations, resistance to ( resistance to ( fluoro) quinolones fluoro) quinolones is is frequently higher’ frequently higher’

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Problems Problems

• The multiple MA for generic (

The multiple MA for generic ( fluoro fluoro-

• )quinolones

)quinolones (low cost) caused by low (low cost) caused by low requirements for their registration requirements for their registration

• It is not understandable why the innovator

It is not understandable why the innovator needs to carry the costs of keeping needs to carry the costs of keeping products on the market (no resistance nor products on the market (no resistance nor environmental data requested by various environmental data requested by various MS), while the generics may MS), while the generics may potentiate potentiate the problem the problem

• Action

Action by by legislator legislator needed needed? ?

• Is

Is the the currently currently implemented implemented EC/ 2004/ 28 EC/ 2004/ 28 the the right right answer answer? ?

12th Oct 2006 12th Oct 2006 EMEA Int. Parties Meeting EMEA Int. Parties Meeting

Action Action Points Points

• More information on use by species

More information on use by species and product would be helpful, and product would be helpful, especially for the ( especially for the ( fluoro fluoro-

• )quinolones

)quinolones. .

• More comparative human use data

More comparative human use data would also be beneficial would also be beneficial

12th Oct 2006 12th Oct 2006 EMEA Int. Parties Meeting EMEA Int. Parties Meeting

Proposal Proposal of AVC

• f AVC
• Use of (

Use of ( fluoro fluoro-

• )quinolones

)quinolones should be under should be under veterinary veterinary prescription only prescription only, following , following veterinary diagnosis veterinary diagnosis, and the products , and the products should not be available as bulk or (foreign should not be available as bulk or (foreign-

• sourced) generics for routine on

sourced) generics for routine on-

• farm use

farm use But: After implementation of 2001/ 82 as But: After implementation of 2001/ 82 as amended by 2004/ 28, now discussion on amended by 2004/ 28, now discussion on exemption criteria for non exemption criteria for non-

• prescription as

prescription as discussed in Brussels this week discussed in Brussels this week E.g E.g.: no .: no vet vet visit visit , , but but a a consultation consultation only

• nly is

is necessary necessary in in some some member member states states ( ( weakens weakens the the vets vets) )

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Proposal Proposal of AVC

• f AVC
• Implementation of “prudent use

Implementation of “prudent use guidelines” and better guidelines” and better penetrating penetrating them to vets and farmers throughout them to vets and farmers throughout the EU and globally the EU and globally

• Make sure that dosage is based on

Make sure that dosage is based on scientific knowledge and proof scientific knowledge and proof

• Limit use to

Limit use to treatment treatment claim of claim of animals animals

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Different ways to approach the Different ways to approach the problem problem

– – Reduce the occurrence of pathogens Reduce the occurrence of pathogens (hygiene) (hygiene) – – Implement strategies to reduce Implement strategies to reduce selection for resistance (correct dose, selection for resistance (correct dose, defined use etc. defined use etc.) ) But But : : monitor monitor via via agreed agreed test test systems systems

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Proposal Proposal

• Appropriate EU agencies and bodies should

Appropriate EU agencies and bodies should collaborate on studies to define more carefully collaborate on studies to define more carefully the most appropriate the most appropriate test system s, sam pling test system s, sam pling strategies and breakpoints strategies and breakpoints to use for to use for resistance determination in organisms isolated resistance determination in organisms isolated from livestock and companion animals that may from livestock and companion animals that may be of public health significance be of public health significance

• Currently

Currently there there are are two two interesting interesting programs programs in in place place: :

• CEESA (European

CEESA (European industry industry) )

• GermVet

GermVet ( ( authorities authorities and and industry industry in Germany) in Germany)

– – Harmonising Harmonising lab test lab test systems systems – – Collecting Collecting properly properly defined defined pathogens pathogens

• Useful

Useful to to have have that that on a EU

• n a EU level

level supported supported by by Framework 7? Framework 7?

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THANK YOU! THANK YOU!

Association of Association of Veterinary Veterinary Consultants Consultants Thanks to David Burch, Peter Watson and Paul McMullin for coordinating the response Board Board Dr Pascal Dr Pascal Richez Richez (F) (F) -

• President

President Dr Klaus Hellman (D) Dr Klaus Hellman (D) -

• Vice

Vice-

• President

President Dr Dr Gert Gert-

• Jan van

Jan van Kesteren Kesteren (NL) (NL) -

• Treasurer

Treasurer Mr Mr Meredith Lloyd Meredith Lloyd-

• Evans (UK)

Evans (UK) -

• Secretary

Secretary E E-

• mail

mail: : gensec.avc@biobridge.co.uk gensec.avc@biobridge.co.uk www.avc.at www.avc.at